Systems, methods and computer program products for guiding the selection of therapeutic treatment regimens

ABSTRACT

Systems, methods and computer program products for guiding selection of a therapeutic treatment regimen for a known disease such as HIV infection are disclosed. The method comprises (a) providing patient information to a computing device (the computer device comprising: a first knowledge base comprising a plurality of different therapeutic treatment regimens for the disease; a second knowledge base comprising a plurality of expert rules for selecting a therapeutic treatment regimen for the disease; and a third knowledge base comprising advisory information useful for the treatment of a patient with different constituents of the different therapeutic treatment regimens; and (b) generating in the computing device a listing (preferably a ranked listing) of therapeutic treatment regimens for the patient; and (c) generating in the computing device advisory information for one or more treatment regimens in the listing based on the patient information and the expert rules.

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.60/080,629 filed Apr. 3, 1998.

A portion of the disclosure of this patent document contains materialthat is the subject of copyright protection. The copyright owner doesnot object to the reproduction of the patent disclosure as it appears inthe public patent files of the United States Patent and TrademarkOffice, but otherwise reserves all other rights in the copyrightedmaterial.

FIELD OF THE INVENTION

This invention concerns systems, methods and computer program productsfor guiding the selection of therapeutic treatment regimens for complexdisorders such as cancer and HIV-1 infection, wherein a ranking ofavailable treatment regimens is generated and advisory informationclinically useful for treating patients is provided.

BACKGROUND OF THE INVENTION

Therapeutic treatment regimens for disorders such as HIV-1 infection(acquired immune deficiency syndrome or AIDS) and cancer areincreasingly complex. New data and new therapeutic treatment regimenscontinue to modify the treatments available, and it is difficult for allbut the specialist to remain current on the latest treatmentinformation. Further, even those who are current on the latest treatmentinformation require time to assimilate that information and understandhow it relates to other treatment information in order to provide thebest available treatment for a patient. Combination therapeutictreatment regimens exacerbate this problem by making potential druginteractions even more complex. Finally, an increasingly sophisticatedpatient population, in the face of a vast volume of consumer informationon the treatment of disease, makes the mere statement of a treatmentregime, without explanation, difficult for the patient to accept.

R. Miller et al., Summary Recommendations for Responsible Monitoring andRegulation of Clinical Software Systems, Ann. Intern. Med. 127, 842-845(1997), describes policy guidelines indicating the desirability ofsystems that generate advice for clinician users in a manner that userscan easily override. Solutions to this need are neither suggested nordisclosed.

M. Pazzani et al., Application of an Expert System in the Management ofHIV-Infected Patients, J. Acquired Immune Deficiency Syndromes and HumanRetrovirology 15, 356-362 (1997) (accepted May 12, 1997), describes arule-based expert system by which protease, reverse transcriptase, andintegrase segments of HIV are cloned and entered into an expert systemthat recommends two, three, and four drug regimens. A means for easilyoverriding the advice given is neither suggested nor disclosed.

U.S. Pat. No. 5,672,154 to Sillen describes a method for giving patientsindividualized, situation-dependent medication advice. The recommendedtype of medicine may include at least two different medicines. No meansfor ranking multiple treatment options is disclosed, and no means forexplaining why treatment options were rejected is given. Rather, thissystem is primarily concerned with generating new rules from patientinformation to optimize a particular therapy for diseases such asParkinson's disease, epilepsy and abnormal blood pressure.

U.S. Pat. No. 5,694,950 to McMichael describes a method and system foruse in treating a patient with immunosuppressants such as cyclosporin.An expert system is employed to generate a recommendation on whether theimmunosuppressant dosage should be changed and, if so, how. Ranking orselection among a plurality of different combination therapeutictreatment regimens is not suggested.

U.S. Pat. No. 5,594,638 to Iliff describes a medical diagnostic systemthat provides medical advice to the general public over a telephonenetwork. This system is not concerned with generating a recommendationfor a combination therapeutic treatment regimen for a known disease (seealso U.S. Pat. No. 5,660,176 to Iliff).

SUMMARY OF THE INVENTION

In view of the foregoing, an object of the invention is to providesystems, methods and computer program products for selecting therapeutictreatment regimens for patients in which available treatments arelisted, and optionally ranked, while unavailable or rejected treatmentregimens (e.g., regimens that would not be effective, or would bedangerous) are not displayed or are assigned a low rank and areindicated to a user as not likely to be efficacious, or not preferreddue to patient-specific complicating factors such as drug interactionfrom concomitant medications.

A further object of the invention is to provide systems, methods andcomputer program products for selecting treatment regimens in which theavailable treatment options can be readily understood.

A further object of the invention is to provide systems, methods andcomputer program products for selecting treatment regimens in which theimplications of selecting a particular treatment regimen can be readilyunderstood.

A further object of the invention is to provide systems, methods andcomputer program products for selecting treatment regimens in which thereasons for rejection of a particular regimen can be readily understood.

A still further object of the invention is to provide systems, methodsand computer program products for obtaining information about theefficacy of previous treatment regimens imposed on patients.

A method of the present invention includes providing patient informationto a computing device that includes various knowledge bases. Forexample, a first knowledge base may include a plurality of differenttherapeutic treatment regimens for a disease or medical condition. Asecond knowledge base may include a plurality of expert rules forselecting a therapeutic treatment regimen for the disease or medicalcondition. A third knowledge base may include advisory informationuseful for the treatment of a patient with different constituents ofdifferent therapeutic treatment regimens. A fourth knowledge base mayinclude information about past therapies, such as how a patient hasfared under previous therapies.

A listing (preferably a ranked listing) of therapeutic treatmentregimens for a patient is generated in the computing device. Advisoryinformation for one or more treatment regimens in the listing isgenerated in the computing device based on the patient information andthe expert rules.

In a preferred embodiment, the method described above further includesentering a user-defined therapeutic treatment regimen for the disease(or medical condition) that may not be displayed from the systemknowledge base-generated therapeutic treatment regimens, and generatingin the computing device advisory information for the user-definedcombination therapeutic treatment regimen.

In addition, in a preferred embodiment, the method described abovefurther includes entering a rejected therapeutic treatment regimen forthe disease (or medical condition) that is included in the firstknowledge base but not recommended from the ranking (or given a very lowranking), and generating in the computing device advisory informationfor the non-recommended/low ranked therapeutic treatment regimen,wherein the advisory information includes at least one reason for notrecommending (or low ranking) the therapeutic treatment regimen.

Further objects and aspects of the present invention are explained indetail in the drawings herein and the specification set forth below.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of the specification, illustrate embodiments of the invention and,together with the description, serve to explain principles of theinvention.

FIG. 1 illustrates a process of the instant invention, includingroutines for entering a user-defined therapeutic treatment regimen andfor entering a "non-recommended" therapeutic treatment regimen.

FIG. 2 schematically illustrates a system or apparatus of the presentinvention.

FIG. 3 illustrates a client-server environment within which the systemof FIG. 2 may operate, according to an embodiment of the presentinvention, and wherein a central server is accessible by at least onelocal server via a computer network, such as the Internet, and whereineach local server is accessible by at least one client.

FIG. 4 illustrates a medical history user interface for entering dataabout a patient's medical history according to the present invention.

FIG. 5 illustrate a user interface chart for monitoring a patient'scondition during a particular therapeutic treatment regimen over aperiod of time according to the present invention.

FIG. 6 illustrates a therapy evaluation user interface that facilitatesevaluation of various therapeutic treatment regimen options with respectto relative efficacy, individualized adjusted relative efficacy, dosage,frequency, cost, medical complications and drug interactions accordingto the present invention.

FIG. 7 illustrates various symbols for providing information about atherapeutic treatment regimen option within the therapy list box of thetherapy evaluation user interface of FIG. 6 according to the presentinvention.

FIG. 8 illustrates the therapy details box of FIG. 6 in "full screen"mode.

FIG. 9 illustrates a pop-up menu including an indexed electronic link toa PDR® that can be activated from within the therapy list box of thetherapy evaluation user interface of FIG. 6 according to the presentinvention.

FIGS. 10A-10D illustrate various functions of the present invention asdescribed in Example 1.

FIGS. 11A-11E illustrate various functions of the present invention asdescribed in Example 2.

FIGS. 12A-12C illustrate various functions of the present invention asdescribed in Example 3.

DETAILED DESCRIPTION OF THE INVENTION

The present invention now will be described more fully hereinafter withreference to the accompanying drawings, in which preferred embodimentsof the invention are shown. This invention may, however, be embodied inmany different forms and should not be construed as limited to theembodiments set forth herein; rather, these embodiments are provided sothat this disclosure will be thorough and complete, and will fullyconvey the scope of the invention to those skilled in the art. Likenumbers refer to like elements throughout.

As will be appreciated by one of skill in the art, the present inventionmay be embodied as a method, data processing system, or computer programproduct. Accordingly, the present invention may take the form of anentirely hardware embodiment, an entirely software embodiment, or anembodiment combining software and hardware aspects. Furthermore, thepresent invention may take the form of a computer program product on acomputer-usable storage medium having computer readable program codemeans embodied in the medium. Any suitable computer readable medium maybe utilized including, but not limited to, hard disks, CD-ROMs, opticalstorage devices, and magnetic storage devices.

The present invention is described below with reference to flowchartillustrations of methods, apparatus (systems), and computer programproducts according to an embodiment of the invention. It will beunderstood that each block of the flowchart illustrations, andcombinations of blocks in the flowchart illustrations, can beimplemented by computer program instructions. These computer programinstructions may be provided to a processor of a general purposecomputer, special purpose computer, or other programmable dataprocessing apparatus to produce a machine, such that the instructions,which execute via the processor of the computer or other programmabledata processing apparatus, create means for implementing the functionsspecified in the flowchart block or blocks.

These computer program instructions may also be stored in acomputer-readable memory that can direct a computer or otherprogrammable data processing apparatus to function in a particularmanner, such that the instructions stored in the computer-readablememory produce an article of manufacture including instruction meanswhich implement the function specified in the flowchart block or blocks.

The computer program instructions may also be loaded onto a computer orother programmable data processing apparatus to cause a series ofoperational steps to be performed on the computer or other programmableapparatus to produce a computer implemented process such that theinstructions which execute on the computer or other programmableapparatus provide steps for implementing the functions specified in theflowchart block or blocks.

A method of the instant invention is illustrated in FIG. 1. In the firststep 10, the patient is examined to determine patient information.Examples of patient information that may be gathered include one or moreof gender, age, weight, CD4⁺ cell information, viral load information,HIV genotype and phenotype information, hemoglobin information,neuropathy information, neutrophil information, pancreatitis, hepaticfunction, renal function, drug allergy and intolerance information, andinformation for drug treatments for other conditions. The informationmay include historical information on prior therapeutic treatmentregimens for the disease or medical condition. While the patient istypically examined on a first visit to determine the patientinformation, it will be appreciated that patient information may also bestored in the computing device, or transferred to the computing devicefrom another computing device, storage device, or hard copy, when theinformation has been previously determined.

The patient information is then provided 11 to a computing device thatcontains a knowledge base of treatments, contains a knowledge base ofexpert rules for determining available treatment options for the patientin light of the patient information, and also contains a knowledge baseof advisory information. A list of available treatments for the patientis then generated 12 from the patient information and the availabletreatments by the expert rules, and advisory information for theavailable treatments is generated 13. The advisory information mayinclude warnings to take the patient off a contraindicated drug orselect a suitable non contraindicated drug to treat the condition beforeinitiating a corresponding treatment regimen and/or informationclinically useful to implement a corresponding therapeutic treatmentregimen.

For example, when the known disease is HIV-1 infection, the treatmentregimen includes antiretroviral drugs, and the treatment regimen oradvisory information may also include contraindicated or potentiallyadversely interacting non-antiretroviral drugs. Particularly, when thetreatment regimen includes a protease inhibitor. A contraindicated drugmay be terfenadine. When the treatment regimen includes indinavir, acontraindicated drug is cisapride.

Exemplary antiretroviral drugs are listed below in Table 1.

                  TABLE 1                                                         ______________________________________                                        Abbreviation Formal Name   Generic Name                                       ______________________________________                                        ABC          ZIAGEN ®  Abacavir                                           ADV          PREVEON ® Adefovir                                           APV          AGENERASE ®                                                                             Amprenavir                                         AZT          RETROVIR ®                                                                              Zidovudine                                         ddI          VIDEX ®   Didanosine                                         ddC          HIVID ®   Zalcitabine                                        d4T          ZERIT ®   Stavudine                                          EFV          SUSTIVA ® Efavirenz                                          3TC          EPIVIR ®  Lamivudine                                         SQV          INVIRASE ®                                                                              Saquinavir                                                      FORTOVASE ®                                                  IDV          CRIXIVAN ®                                                                              Indinavir                                          RTV          NORVIR ®  Ritonavir                                          DLV          RESCRIPTOR ®                                                                            Delavirdine                                        NFV          VIRACEPT ®                                                                              Nelfinavir                                         NVP          VIRAMUNE ®                                                                              Nevirapine                                         ______________________________________                                    

Exemplary advisory information that can be displayed to a user issummarized below in Table 2.

                  TABLE 2                                                         ______________________________________                                                 Description                                                          ______________________________________                                        Drug    The inference engine will process every therapy from a                Therapies                                                                             resource file which contains all valid therapy                        (All the                                                                              combinations. The system will support multiple drug                   output data                                                                           combinations. Those therapies which are recommended by                types below                                                                           the knowledge base will be displayed along with all the               are associat-                                                                         data types below.                                                     ed with a                                                                     therapy)                                                                      Commen- Commentaries consist of warnings and advisories                       taries  concerning drugs as well as various patient conditions.                       Each commentary will appear in specific locations of the                      User Interface. Commentaries will have various Flags,                         Triggers, and Output Locations.                                       Rejection                                                                             Rejection Notices are the explanation why a given therapy             Notices is not recommended. Rejection notices always appear in                        predefined places in the User Interface.                              Cost    The cost per day is calculated for each therapy by the                        inference engine as well as each drug cost within a                           therapy.                                                              Dosage  The base dosage and any adjustments to the base dosage                        due to various patient conditions are calculated by the                       inference engine.                                                     Pill    The number of pills in the therapy.                                   Burden                                                                        Frequency                                                                             Number of times the patient will be taking medications for                    a given therapy. For a multi-drug therapy, the Frequency of                   the therapy is the drug in the therapy that has the highest                   number of Frequencies. If a three-drug regimen has 2 drugs                    with q12h dosages and one that is a q8h, the therapy is                       considered to be a q8h Frequency.                                     Admin   Special drug administration instructions.                             Efficacy                                                                              The relative Efficacy is a whole number that represents the                   relative efficacy of the various therapies. One is the most                   effective therapy.                                                    Adjusted                                                                              The "Adjusted Score" is the Efficacy adjusted up or down              Score   based on patient specific characteristics to roughly                          indicate the likelihood of that therapy being an effective                    treatment for that patient. An example would be: the                          system evaluates a therapy containing a drug that is known                    to be associated with a medical condition in that patient's                   medical history, therefore the therapy is ranked low. The                     Ranking Ordinal is an integer, beginning with 0 and                           having no upper limit. A therapy with a 1 Ranking Ordinal                     (RO = 1) would be ranked at the top of the list whereas a                     therapy with a 10 Ranking Ordinal (RO = 10) would be less                     likely to be successful given the patient's specific history                  and characteristics. Each therapy will have a starting RO                     number which will be the therapy's relative efficacy score.                   The relative efficacy score can then be adjusted up or                        down by the rules. Both base "Efficacy" number and the                        "Adjusted Score" number can be displayed.                             ______________________________________                                    

Diseases (or medical conditions), the treatment of which may befacilitated or improved by the present invention, are those for whichmultiple different therapy options are available for selection andtreatment. Such diseases and medical conditions include, but are notlimited to, cardiovascular disease (including but not limited tocongestive heart failure, hypertension, hyperlipidemia and angina),pulmonary disease (including but not limited to chronic obstructivepulmonary disease, asthma, pneumonia, cystic fibrosis, andtuberculosis), neurologic disease (including but not limited toAlzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis,amyotrophic lateral sclerosis or ALS, psychoses such as schizophreniaand organic brain syndrome, neuroses, including anxiety, depression andbipolar disorder), hepatitis infections (including hepatitis B andhepatitis C infection), urinary tract infections, venereal disease,cancer (including but not limited to breast, lung, prostate, and coloncancer), etc. It should be appreciated that prevention of development oronset of the above-mentioned diseases and medical conditions may befacilitated or improved by the present invention.

The present invention is useful for known diseases such as HIV-1infection (acquired immune deficiency syndrome or "AIDS"), or where theknown disease is any medical condition for which a combinationtherapeutic treatment regimen can be used. The invention is particularlyuseful when the list of available treatments includes a plurality (e.g.,2, 10 or 15 or more) of treatment, combination therapeutic treatmentregimens (e.g., therapeutic treatment regimens incorporating two or moreactive therapeutic agents), where the potential for drug interactions isincreased and/or the complexity involved in selecting the best availabletreatment is multifactorial.

Advantageously, the list of available treatments and advisoryinformation may be regenerated in a number of ways. The patientinformation may be simply modified 18. In addition, if a particulartherapy in which the user might be interested is not presented, auser-defined therapy may be entered 14 and advisory informationgenerated 15 based on the user-defined therapy. Still further, if atherapeutic treatment regimen that is in the knowledge base is rejectedby the system (not recommended upon display), the non-recommendedtherapeutic treatment regimen may be entered 16 and advisory informationgenerated 17 for the non-recommended therapeutic treatment regimen. Thismay indicate to the user that they should discontinue use of anon-critical drug for another condition or select a suitable substitutethat does not create a conflict/non-recommended situation so that theycan then proceed with the therapy of choice. Alternatively, the advisoryinformation can be generated automatically for non-recommendedtherapeutic treatment regimens. These various steps can be repeated inany sequence in an interactive manner to provide the user with assurancethat all treatment options have been given adequate and appropriateconsideration.

The terms "therapy" and "therapeutic treatment regimen" areinterchangeable herein and, as used herein, mean any pharmaceutical ordrug therapy, regardless of the route of delivery (e.g., oral,intraveneous, intramuscular, subcutaneous, intraarterial,intraperitoneal, intrathecal, etc.), for any disease (including bothchronic and acute medical conditions, disorders, and the like). Inaddition, it is understood that the present invention is not limited tofacilitating or improving the treatment of diseases. The presentinvention may be utilized to facilitate or improve the treatment ofpatients having various medical conditions, without limitation.

System Description

The present invention may be embodied as an expert system that providesdecision support to physicians (or other health care providers) treatingpatients with a known disease, such as HIV infection. A system accordingto the present invention calculates combination antiretroviral therapyoptions and attaches all relevant information to those options.

As known to those of skill in the art, an expert system, also known asartificial intelligence (AI), is a computer program that can simulatethe judgment and behavior of a human or an organization that has expertknowledge and experience in a particular field. An expert systemtypically contains a knowledge base containing accumulated experienceand a set of rules for applying the knowledge base to each particularsituation that is described to the program. Expert systems are wellknown to those of skill in the art and need not be described furtherherein.

The antiretroviral therapy options (combinations of antiretroviraldrugs), are derived using a knowledge base consisting of a number ofexpert system rules and functions which in turn take into account agiven patient's treatment history, current condition and laboratoryvalues. A system according to the present invention supports the entry,storage, and analysis of patient data in a large central database. Asystem according to the present invention has a flexible data drivenarchitecture and custom reporting capabilities designed to supportpatient therapy management and clinical drug trial activities such asscreening, patient tracking and support. It is anticipated that a systemaccording to the present invention may be used by health care providers(including physicians), clinical research scientists, and possiblyhealthcare organizations seeking to find the most cost-effectivetreatment options for patients while providing the highest standard ofcare.

A system 20 for carrying out the present invention is schematicallyillustrated in FIG. 2. The system 20 comprises a knowledge base oftreatment regimens 21, which may be ranked for efficacy (e.g., by apanel of experts) or ranked according to system rules, a knowledge baseof expert rules 22, a knowledge base of advisory information 23, aknowledge base of patient therapy history 24 and patient information 25.Patient information is preferably stored within a database and isconfigured to be updated. The knowledge bases and patient information21-25 may be updated by an input/output system 29, which can comprise akeyboard (and/or mouse) and video monitor. Note also that, while theknowledge bases and patient data 21-25 are shown as separate blocks, theknowledge bases and patient data 21-25 can be combined together (e.g.,the expert rules and the advisory information can be combined in asingle database).

To carry out the method described above, the information from blocks21-25 is provided to an inference engine 26, which generates the listingof available treatments and the corresponding advisory information fromthe information provided by blocks 21-25. The inference engine 26 may beimplemented as hardware, software, or combinations thereof. Inferenceengines are known and any of a variety thereof may be used to carry outthe present invention. Examples include, but are not limited to, thosedescribed in U.S. Pat. No. 5,263,127 to Barabash et al. (Method for fastrule execution of expert systems); U.S. Pat. No. 5,720,009 to Kirk etal. (Method of rule execution in an expert system using equivalenceclasses to group database objects); U.S. Pat. No. 5,642,471 to Paillet(Production rule filter mechanism and inference engine for expertsystem); U.S. Pat. No. 5,664,062 to Kim (High performance max-mincircuit for a fuzzy inference engine).

High-speed inference engines are preferred so that the results of dataentered are continually updated as new data is entered. As with theknowledge bases and patient information in blocks 21-25, the inferenceengine 26 may be a separate block from the knowledge bases and patientinformation blocks 21-25, or may be combined together in a commonprogram or routine.

Note that the advisory information that is generated for any availabletherapy may differ from instance to instance based on differences in thepatient information provided.

System Architecture

The present invention can be implemented as a system running on a standalone computing device. Preferably, the present invention is implementedas a system in a client-server environment. As is known to those ofskill in the art, a client application is the requesting program in aclient-server relationship. A server application is a program thatawaits and fulfills requests from client programs in the same or othercomputers. Client-server environments may include public networks, suchas the Internet, and private networks often referred to as "intranets",local area networks (LANs) and wide area networks (WANs), virtualprivate networks (VPNs), frame relay or direct telephone connections. Itis understood that a client application or server application, includingcomputers hosting client and server applications, or other apparatusconfigured to execute program code embodied within computer usablemedia, operates as means for performing the various functions andcarries out the methods of the various operations of the presentinvention.

Referring now to FIG. 3, a client-server environment 30 according to apreferred embodiment of the present invention is illustrated. Theillustrated client-server environment 30 includes a central server 32that is accessible by at least one local server 34 via a computernetwork 36, such as the Internet. A variety of computer networktransport protocols including, but not limited to TCP/IP, can beutilized for communicating between the central server 32 and the localservers 34.

Central Server

The central server 32 includes a central database 38, such as theMicrosoft® SQL Server application program, version 6.5 (available fromMicrosoft, Inc., Redmond, Wash.), executing thereon. The central server32 ensures that the local servers 34 are running the most recent versionof a knowledge base. The central server 32 also stores all patient dataand performs various administrative functions including adding anddeleting local servers and users to the system (20, FIG. 2). The centralserver 32 also provides authorization before a local server 34 can beutilized by a user. Patient data is preferably stored on the centralserver 32, thereby providing a central repository of patient data.However, it is understood that patient data can be stored on a localserver 34 or on local storage media.

Local Server

Each local server 34 typically serves multiple users in a geographicallocation. Each local server 34 includes a server application, aninference engine, one or more knowledge bases, and a local database 39.Each local server 34 performs artificial intelligence processing forcarrying out operations of the present invention. When a user logs on toa local server 34 via a client 35, the user is preferably authenticatedvia an identification and password, as would be understood by thoseskilled in the art. Once authenticated, a user is permitted access tothe system (20, FIG. 2) and certain administrative privileges areassigned to the user.

Each local server 34 also communicates with the central server 32 toverify that the most up-to-date version of the knowledge base(s) andapplication are running on the requesting local server 34. If not, therequesting local server 34 downloads from the central server 32 thelatest validated knowledge base(s) and/or application before a usersession is established. Once a user has logged onto the system (20, FIG.2) and has established a user session, all data and artificialintelligence processing is preferably performed on a local server 34. Anadvantage of the illustrated client-server configuration is that most ofthe computationally intensive work occurs on a local server 34, therebyallowing "thin" clients 35 (i.e., computing devices having minimalhardware) and optimizing system speed.

In a preferred embodiment, each local server database 39 is implementedvia a Microsoft® SQL Server application program, Version 6.5. Theprimary purpose of each local database 39 is to store various patientidentifiers and to ensure secure and authorized access to the system(20, FIG. 2) by a user. It is to be understood, however, that bothcentral and local databases 38, 39 may be hosted on the central server32.

Local Client

Each local client 35 also includes a client application program thatconsists of a graphical user interface (GUI) and a middle layer programthat communicates with a local server 34. Program code for the clientapplication program may execute entirely on a local client 35, or it mayexecute partly on a local client 35 and partly on a local server 34. Aswill be described below, a user interacts with the system (20, FIG. 2)by entering (or accessing) patient data within a GUI displayed withinthe client 35. The client 35 then communicates with a local server 34for analysis of the displayed patient information.

Computer program code for carrying out operations of the presentinvention is preferably written in an object oriented programminglanguage such as JAVA®, Smalltalk, or C++. However, the computer programcode for carrying out operations of the present invention may also bewritten in conventional procedural programming languages, such as the"C" programming language, in an interpreted scripting language, such asPerl, or in a functional (or fourth generation) programming languagesuch as Lisp, SML, or Forth.

The middle layer program of the client application includes an inferenceengine within a local server 34 that provides continuous on-linedirection to users, and can instantly warn a user when a patient isassigned drugs or a medical condition that is contraindicated with, orantagonistic of, the patient's current antiretroviral therapy. Everytime patient data is entered into the system (20, FIG. 2) or updated, oreven as time passes, the inference engine evaluates the current statusof the patient data, sorting, categorizing, ranking and customizingevery possible antiretroviral therapy for a patient according to thespecific needs of the patient.

Inference Engine

Inference engines are well known by those of skill in the art and neednot be described further herein. Each knowledge base used by aninference engine according to the present invention is a collection ofrules and methods authored by a clinical advisory panel of HIV-treatingphysicians and scientists. A knowledge base may have subjective rules,objective rules, and system-generated rules. Objective rules are basedon industry established facts regarding the treatment of HIV usingantiretroviral therapy and are drawn from the package insert informationof antiretroviral drug manufacturers and from peer reviewed andpublished journal articles. An example of an objective rule would be anantiretroviral to antiretroviral contraindication such as:

Rule #1: If the eval therapy contains Zidovudine (AZT) and Stavudine(d4T), then reject the therapy.

In Rule #1, the term "eval therapy" refers to the therapy currentlybeing analyzed by the system (20, FIG. 2). Rule #1 then states that ifthis therapy contains both AZT and d4T, then this therapy should not bedisplayed in a list of potential therapy options for the patient.

For objective rules, the present invention can be configured so as toprevent a user from receiving recommendations on new therapy optionswhen certain crucial data on the patient has not been entered. However,it is understood that the present invention does not prevent a healthcare provider, such as a physician, from recording his/her therapydecisions, even if the system (20, FIG. 2) has shown reasons why thattherapy may be harmful to the patient. The present invention allows ahealth care provider to be the final authority regarding patienttherapy.

Subjective rules are based on expert opinions, observations andexperience. Subjective rules are typically developed from "bestpractices" information based on consensus opinion of experts in thefield. Such expert opinion may be based on knowledge of the literaturepublished or presented in the field or their own experience fromclinical practice, research or clinical trials of approved andunapproved medications. A number of experts are used so that personalbias is reduced.

System generated rules are those derived from the outcomes of patientstracked in the system who received known and defined therapies andeither improved, stabilized or worsened during a defined period. Becauseof the large number of potential combinations usable in HIV infection,this system generated database and rules derived from them are likely toencompass data beyond that achievable from objective or subjective rulesdatabases.

The rules which comprise the various knowledge bases (21-24, FIG. 2) ofthe present invention each have two main parts: a premise and aconclusion--also referred to as the left side and the right side,respectively. When a premise of a rule is found to be true, the actionspecified in the conclusion is taken. This is known to those of skill inthe art as "firing" the rule. For example, consider the following rule:

    ______________________________________                                        Rule ID   Premise            Conclusion                                       ______________________________________                                        FiltDComA1 - -                                                                          If the eval therapy contains ddC -                                                               Commentary 18                                    ______________________________________                                    

The premise of the above rule is for the inference engine to determinewhether or not a therapy being evaluated (i.e., "eval therapy" )contains the antiretroviral drug "ddC" . If a therapy does contain theantiretroviral drug ddC, the action called for by the conclusion of therule is to attach "Commentary 18" to the therapy. Commentary 18 may be apiece of text that provides a user with the necessary information abouttherapies containing ddC.

Exemplary rules which may comprise one or more knowledge bases accordingto the present invention are listed below in Table 3.

                  TABLE 3                                                         ______________________________________                                        Therapy initiation/change: Rules that provide information on                  therapy change or initiation                                                  Boundary condition rules: Limits for values, intervals for values to          be updated                                                                    Comment Data Aging rules: These rules warn the user that the data             in certain fields is getting old and that the most current values in the      system will be used.                                                          Rules that filter therapies due to drug interactions in ARV drug              combinations                                                                  Rules that filter therapies due to medical conditions                         Rules that filter therapies due to genotypic mutations in patient's           plasma HIV                                                                    Rules that filter therapies due to phenotypic sensitivity/resistance          Antiretroviral therapy ranking rules                                          General dosage rules                                                          Solid dosage rule                                                             Dosage modifications due to ARV-ARV drug combination                          Dosage modification due to ARV-NonARV interaction                             Dosage modification due to medical condition                                  Comment determined                                                            General commentary rules                                                      Commentaries added due to medical conditions                                  Commentaries added due to drug interactions                                   Commentaries added due to drug combination                                    Delivery size rules                                                           ______________________________________                                    

Using the various knowledge bases and patient information of the presentinvention (21-25, FIG. 2), the inference engine (26, FIG. 2) canevaluate potential therapy options for a patient based on a patient'smedical history (including therapy history) and current laboratoryvalues. Accordingly multiple antiretroviral drug combinations can bequickly and accurately analyzed for a particular patient. Furthermore,the inference engine can quickly provide guidance in the areas listedbelow in Table 4.

                  TABLE 4                                                         ______________________________________                                        Data Integrity                                                                             Is the patient lab and assessment data getting                                too old to be considered reliable? Are there                                  conflicts between lab data such as phenotype                                  data which indicates resistance to one or more                                antiretroviral drugs in the patient's current                                 therapy and current viral load data which                                     indicates significant viral suppression?                         Therapy      Should antiretroviral therapy be initiated for                   Performance  the patient? Is the patient's current therapy                                 achieving good initial and long-term viral                                    suppression or should the therapy be changed?                                 Are there potential non-compliance issues as                                  demonstrated by a lack of viral suppression                                   with a regimen when current genotype or                                       phenotype data does provide explanation for                                   the failure by demonstrating resistance to any                                drugs in the patient current therapy?                            Dosage       What are the base and adjusted dosages of                                     antiretroviral drugs in a given therapy? Are                                  there any special specific dosage                                             administration instructions?  What are options                                if patient can only take liquid dosage forms?                    Contra-      Which antiretroviral drugs can be used with                      indications  each other and what dosage adjustments are                                    required? Are there any contraindications or                                  interactions between antiretroviral drugs in                                  patient's current therapy or potential therapies                              and the non-antiretroviral drugs patient is                                   taking and if so what are they and what, if any,                              dosage adjustments are required?                                 Medical      Are there any medical conditions to be aware                     Conditions   of in deciding an appropriate therapy for                                     patient? What, if any, effect do current or                                   historical medical conditions have on each                                    therapy option?                                                  Drug Cost and                                                                              How much does each therapy option cost?                          Delivery Data                                                                              What is the dosing frequency of the drugs in                                  the therapy? What is the pill count and                                       optimum delivery size for the least number of                                 pills?                                                           Therapy      What are all the drug combination therapy                        Options      options for patient? How can physician                                        instantly assess which of the hundreds of                                     potential combinations will be the most                                       effective for patient? What information from                                  the package inserts from each drug apply                                      specifically to patient? What is the relative                                 antiviral efficacy of each therapy? Are there                                 special considerations that might make one                                    therapy more or effective for patient?                           Resistance   What drugs are patient's virus current                                        genotypic or phenotypic profile known to be                                   associated with resistance to? Which                                          antiretroviral drugs are more effective against                               resistant strains when used together? Which                                   drugs (if any) used in historical therapies are                               most likely to be effective if recycled into a                                new therapy? Can any of the drugs in patient's                                current therapy be recycled into the next                                     therapy?                                                         ______________________________________                                    

User Interface

Referring now to FIGS. 4-9, exemplary user interfaces according to thepresent invention will be illustrated. In FIG. 4, a medical history userinterface 50 for entering data about a patient's medical historyaccording to the present invention is illustrated. The medical historyuser interface 50 can be displayed by activating the "Medical History"tab 50a. The illustrated medical history user interface 50 allows a userto create, save, update and print patient records. When a user adds anew patient, the medical history user interface 50 appears with emptydata entry fields. Data entry fields for receiving information via a GUIare well known to those of skill in the art and need not be describedfurther herein. When a user opens a patient record for editing, themedical history user interface 50 appears with patient data in thevarious fields. Preferably color is used to highlight critical orrequired information in a patient record.

Important elements in the illustrated medical history user interface 50include a "print" button 51 for printing a patient record andtherapeutic treatment regimen details; a "save" button 52 for saving apatient record; and a "speed entry" check box 53 for allowing a user tomove quickly between entry fields. In addition, there are multiple groupheadings 54 that divide a patient's medical history into relatedcategories. Each group contains entry fields in which a user can addpatient information. An "add" button 55 allows a user to add newinformation to a patient record for a selected group. A "delete" button56 allows a user to delete patient information for a selected group(although the original information is still recorded in the database). A"history" button 57 allows a user to review a patient's historical datafor each selected group.

After completing a patient's medical history, an inference engineanalyzes the data and suggests whether a therapeutic treatment regimenis indicated; if an existing therapeutic treatment regimen should becontinued or changed; and the best drug therapies for the selectedpatient. Often, more than one drug therapy is presented to the user.These drug therapies are preferably ranked according to expectedefficacy, frequency in dosage, pill count, and cost. All of thesefactors can help the user make a decision about what therapy to use forthe selected patient. When a user clicks on a drug therapy in thepresented list, information is provided about the dosage regimens. Also,various warnings, such as drug interaction warnings, and notes abouteach drug, are presented. An appropriate drug therapy can then beselected.

In FIG. 5, an exemplary user interface chart 60 for monitoring apatient's condition during a particular drug therapy over a period oftime is illustrated. The user interface chart 60 can be displayed byactivating the "Chart" tab 60a. The illustrated user interface chart 60tracks the CD4 level against viral load. Along the left-hand side of theY-axis 61 the CD4 count is plotted. Along the right-hand side of theY-axis 61 the viral load count is plotted. The lines 62 represent theCD4 test and the viral load test as would be understood by those havingskill in the art. Drug therapy for a time period is indicated within thearea of the chart user interface 60 indicated as 63. Time is plottedalong the X-axis 64, as illustrated.

In FIG. 6, a therapy evaluation user interface 70 that facilitatesevaluation of various therapy options with respect to relative efficacy,dosage, frequency, cost, medical complications and drug interactions isillustrated. The therapy evaluation user interface 70 can be displayedby activating the "Therapy Evaluation" tab 70a. Important elements inthe illustrated therapy evaluation user interface 70 include an"Evaluate Current Therapy" button 71 for initiating an evaluation of acurrent therapy and a "Current Therapy" field 72 that lists a patient'scurrent therapy. Detailed information about a patient's therapy isdisplayed in the therapy details box 73. A therapy displayed within box73 is identified in box 74.

Multiple check boxes 75 are provided that allow a user to control howinformation is displayed within the therapy evaluation user interface70. Within the therapy list box 76, a list of available therapies for apatient can be displayed. In the illustrated embodiment the drugs arelisted in standard abbreviated form. Other information displayed witheach drug may include that listed below in Table 5.

                  TABLE 5                                                         ______________________________________                                        Efficacy    Lists the therapy according to expected                           Rating      effectiveness only, regardless of patient specific                            considerations (1 is most effective).                             Adjusted Score                                                                            This number uses the Efficacy Rating as a base                                and then the system adjusts it up or down based                               on patient specific conditions (1 is most                                     effective).                                                       Safety      A brief two or three word summary of the alerts                   Considerations                                                                            associated with the therapy.                                      Frequency   Lists the dosage frequency (q12h, q24h, etc.).                    Pills       Lists the total number of pills required per day for                          the complete regimen.                                             Cost        Lists the total cost of the regimen per day.                      Medical Alert                                                                             Displays a Y if there is one or more Yellow                                   Medical Alerts and an R if there is one or more                               Red Medical Alerts associated with the therapy.                   Drug        Displays a Y if there is one or more Yellow Drug                  Interaction Interaction Alerts and an R if there is one or more                           Red Drug Interaction Alerts associated with the                               therapy.                                                          ______________________________________                                    

A list of available antiretroviral drugs is displayed within box 77. Auser desiring to evaluate a particular combination of drugs can clickthe appropriate check boxes 77a to review information in the therapydetails box 73. A "Use as Current Therapy" button 78 allows a user toapply a particular therapy to a patient. Various hyperlinks 79 withinthe therapy details box 73 allow a user to display specific informationabout a therapy evaluation. For example, a user can be allowed to view arule which is associated with the displayed text.

Resistance evaluation alerts 80 can be provided adjacent each availableantiretroviral drug displayed within box 77. For example, a blue "G"icon can be used to indicate that a patient's last genotype testcontains mutations which are known to be associated with full or partialresistance to the antiretroviral drug. A red "P" icon can be used toindicate that a patient's last phenotype test demonstrates resistance tothe antiretroviral drug.

Within the therapy list box 76, various symbols (described in FIG. 7)can be utilized to provide information about a drug therapy option.These symbols provide an instant graphical warning level for eachtherapy option. Some symbols, such as a red exclamation point, indicatethat there is critical, possibly life threatening information in thetherapy details box 73 for that therapy which must be read in order forthat therapy to be properly utilized.

When a drug therapy from the therapy list box 76 is selected by a userfor evaluation, the therapy details box 73 of FIG. 6 can be displayed in"full screen" mode as illustrated in FIG. 8. Important elements in theillustrated therapy details box 73 include an identification box 73a foridentifying the therapy being evaluated; a "Use as Current Therapy"button 78 that allows a user to apply a particular therapy to a patient;and a "Show Therapies" button 73b that returns the therapy details box73 back to half-screen size as illustrated in FIG. 6. In addition,various hyperlinks may be embedded within text displayed within thetherapy details box 73 that can be activated by a user to displayvarious types of information. Eye catching alert banner(s) 73c and text73d can be displayed at the top of the therapy details box 73 asillustrated. Dosages 73e of each drug, along with special administrationinstructions, can be displayed within the therapy details box 73 asillustrated. Dosage adjustment information 73f and various warnings andadvisories 73g can also be displayed within the therapy details box 73as illustrated.

According to a preferred embodiment of the present invention,therapeutic treatment regimens are not displayed to a user if an invaliddrug is selected for treatment of a patient.

Physicians Desk Reference®

According to a preferred embodiment of the present invention, thePhysicians Desk Reference® (PDR®) 28, which is a known drug referencesource, is fully integrated with the system 20 of FIG. 2. Users canaccess the PDR® drug abstracts for antiretroviral drugs listed in thetherapy list box 76 of the therapy evaluation user interface 70 of FIG.6. In addition, users can access the PDR® on-line Web database to obtainadditional information about a specific drug or to research a substitutefor a contraindicated drug. When a user selects a drug within thetherapy list box 76 of the therapy evaluation user interface 70, a webbrowser preferably is launched and the PDR® on-line Web database isaccessed. Information can also be extracted from the PDR® on-line Webdatabase to provide drug selection lists for non-antiretroviral drugsthat a patient may be taking and to define relationships between brandname and generic drugs.

As illustrated in FIG. 9, a PDR® pop-up menu 90 may be provided that canbe activated from within the therapy list box 76 of the therapyevaluation user interface 70 of FIG. 6. From the PDR® pop-up menu 90 auser can access various information from the PDR® including, but notlimited to, drug abstracts, and generic components contained within abrand name drug.

The following non-limiting examples illustrate various aspects of thepresent invention. These examples are provided for illustrative purposesonly, and are not intended to be limiting of the invention.

EXAMPLE 1

Example 1 will be explained with reference to FIGS. 10A-10D. Referringto FIG. 10A, a medical history user interface 50 containing evaluateddata for patient "demo1" is illustrated. The group heading "Hemoglobin"54a has changed colors to indicate to a user that the patient has anabnormally low hemoglobin value from a previous (historical) bloodsampling. When the therapy evaluation tab 70a is activated to displaythe therapy evaluation user interface 70 (FIG. 10B) the associatedmedical condition warning of a history of anemia and the cautionnotification if using drugs known to be associated with hematopoetictoxicity is triggered as illustrated in the therapy details box 73 ofFIG. 10B.

In addition, the group heading "Renal Function" 54b in FIG. 10a haschanged colors to warn a user of potential renal dysfunction and is alsoindicated by the low estimated creatinine clearance rate in field F1(which the system calculates using a mathematical formula taking patientage, sex, weight, and serum creatinine values--all of which are fieldsof the "Medical History" user interface 50). This information is pointedout to the user and is used if dosage adjustments are required for drugsthat are known to be affected (cleared) by renal function.

Current and the next most recent CD4⁺ cell count and viral load aredisplayed (F2, medical history user interface 50). This information isalso used to determine when to start or change therapy and to evaluatethe initial antiviral efficacy of a newly administered antiviralregimen.

Current and historical values for all fields in the medical history userinterface 50 (FIG. 10A) can be viewed by pressing the "H" button besidefields that have this button.

In FIG. 10C, the "Chart" user interface 60 has been activated. HIV RNA(viral load) is plotted on a log scale, the CD4 count is plotted on alinear scale, and the drug treatments are shown as Gantt bars on thehorizontal date scale at the bottom of the chart user interface 60.

In FIG. 10D, the "Change Therapy Recommendation" message box MB1 pops upwhen the "Therapy Evaluation" tab 70a is selected. This box representsthe processing of the data from the "Medical History" tab and theknowledge base output, including objective rules derived from publishedtreatment guidelines, indicating that initiation of therapy, or a changeof therapy in this case, may be called for if the other variable(s)indicated in the message have been addressed.

The list of available therapies and associated ranking order may beshown within the therapy details box 73 of FIG. 10B. This represents theoutput of the knowledge base for therapy selection. Included with thelist of therapies can be any of the following: safety advisories (dosageadjustment, drug interaction, etc.) with a yellow triangle or redexclamation warning symbols; number of pills; daily cost of all threedrugs; dosing regimen (q 8h, q 12 h, etc.); and dosages for all drugs ina regimen (including dosage adjustments if necessary) and pertinentinformation specific to the patient is listed in the dialog box.

EXAMPLE 2

Example 2 will be explained with reference to FIGS. 11A-11E, and relatesto patient file "ARV naivel" which is an example of an HIV-infectedpatient who has not been treated with anti-HIV drugs previously. In FIG.11A, a medical history user interface 50 containing evaluated data forpatient "ARV naive1" is illustrated. In FIG. 11B, when the "TherapyEvaluation" tab 70a is activated to display the therapy evaluation userinterface 70, a "Boundary and Prequalification Messages" message box MB2pops up indicating that according to the current, published, HIVtreatment guidelines, the patient should be initiated on antiviraltherapy and that the current guidelines recommend combinational therapy.

In FIG. 11C, the therapy evaluation user interface 70 has been activatedand demonstrates features/functions associated with therapy evaluationincluding a general warning W1 and advisories A1, A2, and A3 for thepatient related to treatment of the disease (e.g., whether therapyshould be initiated or changed) or related to a specific therapyselected from the list box which is being evaluated by the user.

FIG. 11D illustrates various information that is displayable by clickingon an individual therapy in the therapy list box 76 of FIG. 11C.Information displayed includes dosages of all drugs with general andpatient-specific warnings and advisories.

The features available by right clicking on any therapy listed in thetherapy list box 76 of FIG. 11C are illustrated in FIG. 11E and include:linking to an electronic PDR® to show drug package insert information orperform drug search information; showing or hiding columns ofinformation displayed within the therapy list box; linking to apublication or abstract associated with a therapy that has a "book" iconassociated therewith; and various printing functions.

EXAMPLE 3

Example 3 will be explained with reference to FIGS. 12A-12C, and relatesto patient file "Features1" which illustrates some importantfunctions/features that a system according to the present invention canprovide for highly drug experienced patients who may have developedresistance associated with the use of several antiviral drugs. Features,including functions attributed to the new resistance and historicaltherapy rules are illustrated and includes:

1) Potential drug resistance advisories (A1, FIG. 12A) when the charttab 60a is activated, or (A2, FIG. 12B) when the therapy evaluation tab70a is activated;

2) The heads up "P" and "G" indicators (I1 and I2, FIG. 12B) to remindof phenotypic or genotypic resistance associated with certain anti-HIVcompounds as demonstrated for this patient (including indication ofexpected/anticipated genotypic resistance, as a result ofcross-resistance, to a drug that a patient may not be taking currentlyor has not previously taken);

3) The drug interaction warning system (indicated by warning W3, FIG.12C). Warning W3 is for the interaction between Nevirapine and rifabutin(which was selected from the list of non-antiretroviral drugs availableas part of the medical history user interface 50). The drug interactionwarning message may be viewed from the medical history user interface 50by "right-clicking" the non-ARV title bar 54C, which has turned yellowindicating the presence of an ARV-nonARV drug interaction. Thisinformation is also prominently displayed for the user on the therapyevaluation user interface 70 as a text message (W3, FIG. 12B) as well asin the "Safety Considerations" section of the drug list box (76, FIG.12B); and

4) The chart user interface 60 (FIG. 12A) illustrates the viral load,CD4, drug therapies, and associated drug resistance in graphic form forthe user to evaluate.

The foregoing is illustrative of the present invention and is not to beconstrued as limiting thereof. Although a few exemplary embodiments ofthis invention have been described, those skilled in the art willreadily appreciate that many modifications are possible in the exemplaryembodiments without materially departing from the novel teachings andadvantages of this invention. Accordingly, all such modifications areintended to be included within the scope of this invention as defined inthe claims. Therefore, it is to be understood that the foregoing isillustrative of the present invention and is not to be construed aslimited to the specific embodiments disclosed, and that modifications tothe disclosed embodiments, as well as other embodiments, are intended tobe included within the scope of the appended claims. The invention isdefined by the following claims, with equivalents of the claims to beincluded therein.

That which is claimed is:
 1. A method for guiding the selection of atherapeutic treatment regimen for a patient with a known disease ormedical condition, said method comprising:(a) providing patientinformation to a computing device comprising:a first knowledge basecomprising a plurality of different therapeutic treatment regimens forsaid disease or medical condition; a second knowledge base comprising aplurality of expert rules for evaluating and selecting a therapeutictreatment regimen for said disease or medical condition; a thirdknowledge base comprising advisory information useful for the treatmentof a patient with different constituents of said different therapeutictreatment regimens; and (b) generating in said computing device a rankedlisting of available therapeutic treatment regimens for said patient;and (c) generating in said computing device advisory information for oneor more therapeutic treatment regimens in said ranked listing based onsaid patient information and said expert rules.
 2. A method according toclaim 1, further comprising the steps of:(d) entering a user-definedtherapeutic treatment regimen for said disease or medical condition thatis not included in said first knowledge base; (e) generating in saidcomputing device advisory information for said user-defined combinationtherapeutic treatment regimen.
 3. A method according to claim 1, furthercomprising the steps of:(f) entering a non-recommended therapeutictreatment regimen for said disease or medical condition that is includedin said first knowledge base but not recommended from said rankedlisting; and (g) generating in said computing device advisoryinformation for said non-recommended therapeutic treatment regimen, saidadvisory information including at least one reason fornon-recommendation of said therapeutic treatment regimen.
 4. A methodaccording to claim 1, said patient information comprising gender, age,weight, CD4 information, viral load information, HIV genotype andphenotype information, hemoglobin information, neuropathy information,neutrophil information, pancreatitis, hepatic function, renal function,drug allergy and intolerance information.
 5. A method according to claim1, said patient information including prior therapeutic treatmentregimen information.
 6. A method according to claim 1, wherein saidpatient information includes prior patient information stored in saidcomputing device.
 7. A method according to claim 1, said advisoryinformation including:warnings to take the patient off a contraindicateddrug before initiating a corresponding therapeutic treatment regimen;and information clinically useful to implement a correspondingtherapeutic treatment regimen.
 8. A method according to claim 1, whereinsaid computing device comprises a fourth knowledge base comprisingpatient therapeutic treatment regimen history, said advisory informationincluding previous therapeutic treatment regimen information extractedfrom said fourth knowledge base.
 9. A method according to claim 7,wherein said known disease or medical condition is HIV-1 infection, saidtherapeutic treatment regimen includes antiretroviral drugs, and saidtherapeutic treatment regimen includes contraindicated or potentiallyadversely interacting non-antiretroviral drugs.
 10. A method accordingto claim 7, wherein said therapeutic treatment regimen includes aprotease inhibitor, and said contraindicated drug is terfenadine.
 11. Amethod according to claim 7, wherein said therapeutic treatment regimenincludes indinavir and said contraindicated drug is cisapride.
 12. Amethod according to claim 1, wherein said known disease or medicalcondition is one where multiple prophylactic or therapeutic treatmentregimens are available to be used singly or in combination in thetreatment of said disease.
 13. A method according to claim 1, whereinsaid known disease or medical condition is a cardiovascular disease. 14.A method according to claim 1, wherein said known disease or medicalcondition is a pulmonary disease.
 15. A method according to claim 1,wherein said known disease or medical condition is a neurologic disease.16. A method according to claim 1, wherein said known disease or medicalcondition is cancer.
 17. A method according to claim 1, wherein saidknown disease or medical condition is a urinary tract infection.
 18. Amethod according to claim 1, wherein said known disease or medicalcondition is hepatitis.
 19. A method according to claim 1, wherein saidknown disease or medical condition is HIV-1 infection.
 20. A methodaccording to claim 1, wherein said first knowledge base comprises aplurality of different combination therapeutic treatment regimens.
 21. Amethod according to claim 1, wherein drug dosage information isrecommended and adjusted if necessary depending upon said patientinformation.
 22. A method according to claim 1, further comprising thestep of:(d) accessing, via said computing device, information for one ormore therapeutic treatment regimens from a drug reference source.
 23. Asystem for guiding the selection of a therapeutic treatment regimen fora patient with a known disease or medical condition, said systemcomprising:(a) a computing device comprising:a first knowledge basecomprising a plurality of different therapeutic treatment regimens forsaid disease or medical condition; a second knowledge base comprising aplurality of expert rules for selecting a therapeutic treatment regimenfor said disease or medical condition; a third knowledge base comprisingadvisory information useful for the treatment of a patient withdifferent constituents of said different therapeutic treatment regimens;and (b) means for providing patient information to said computingdevice; (c) means for generating in said computing device a rankedlisting of therapeutic treatment regimens for said patient; and (d)means for generating in said computing device advisory information forone or more therapeutic treatment regimens in said ranked listing basedon said patient information and said expert rules.
 24. A systemaccording to claim 23, further comprising:(e) means for entering auser-defined therapeutic treatment regimen for said disease or medicalcondition that is not generated or displayed via said first knowledgebase; (f) means for generating in said computing device advisoryinformation for said user-defined combination therapeutic treatmentregimen.
 25. A system according to claim 23, further comprising:(f)means for entering a non-recommended therapeutic treatment regimen forsaid disease or medical condition that is included in said firstknowledge base but not recommended from said ranked listing; and (g)means for generating in said computing device advisory information forsaid non-recommended therapeutic treatment regimen, said advisoryinformation including at least one reason for non-recommendation of saidtherapeutic treatment regimen.
 26. A system according to claim 23, saidpatient information comprising gender, age, weight, CD4 information,viral load information, HIV genotype and phenotype information,hemoglobin information, neuropathy information, neutrophil information,pancreatitis, hepatic function, renal function, drug allergy andintolerance information.
 27. A system according to claim 23, saidpatient information including prior therapeutic treatment regimeninformation.
 28. A system according to claim 23, wherein said patientinformation includes prior patient information stored in said computingdevice.
 29. A system according to claim 23, said advisory informationincluding:warnings to take the patient off a contraindicated drug beforeinitiating a corresponding therapeutic treatment regimen; andinformation clinically useful to implement a corresponding therapeutictreatment regimen.
 30. A system according to claim 23, wherein saidcomputing device comprises a fourth knowledge base comprising patienttherapeutic treatment regimen history, said advisory informationincluding previous therapeutic treatment regimen information extractedfrom said fourth knowledge base.
 31. A system according to claim 29,wherein said known disease or medical condition is HIV-1 infection, saidtherapeutic treatment regimen includes antiretroviral drugs, and saidtherapeutic treatment regimen includes contraindicated or potentiallyadversely interacting non-antiretroviral drugs.
 32. A system accordingto claim 29, wherein said therapeutic treatment regimen includes aprotease inhibitor, and said contraindicated drug is terfenadine.
 33. Asystem according to claim 29, wherein said therapeutic treatment regimenincludes indinavir and said contraindicated drug is cisapride.
 34. Asystem according to claim 23, wherein said known disease or medicalcondition is one where multiple prophylactic therapeutic treatmentregimens are available to be used singly or in combination in thetreatment of said disease or medical condition.
 35. A system accordingto claim 23, wherein said known disease or medical condition is acardiovascular disease.
 36. A system according to claim 23, wherein saidknown disease or medical condition is a pulmonary disease.
 37. A systemaccording to claim 23, wherein said known disease or medical conditionis a neurologic disease.
 38. A system according to claim 23, whereinsaid known disease or medical condition is cancer.
 39. A systemaccording to claim 23, wherein said known disease or medical conditionis a urinary tract infection.
 40. A system according to claim 23,wherein said known disease or medical condition is hepatitis.
 41. Asystem according to claim 23, wherein said known disease or medicalcondition is HIV-1 infection.
 42. A system according to claim 23,wherein said first knowledge base comprises a plurality of differentcombination therapeutic treatment regimens.
 43. A system according toclaim 23, wherein drug dosage information is recommended and adjusted ifnecessary depending upon said patient information.
 44. A systemaccording to claim 23, further comprising:(e) means for accessing, viasaid computing device, information for one or more therapeutic treatmentregimens from a standard drug reference source.
 45. A computer programproduct for guiding the selection of a therapeutic treatment regimen fora patient with a known disease or medical condition, said computerprogram product comprising a computer usable storage medium havingcomputer readable program code means embodied in the medium, thecomputer readable program code means comprising:(a) computer readableprogram code means for generating:a first knowledge base comprising aplurality of different therapeutic treatment regimens for said diseaseor medical condition; a second knowledge base comprising a plurality ofexpert rules for selecting a therapeutic treatment regimen for saiddisease or medical condition; a third knowledge base comprising advisoryinformation useful for the treatment of a patient with differentconstituents of said different therapeutic treatment regimens; and (b)computer readable program code means for providing patient information;(c) computer readable program code means for generating a ranked listingof available therapeutic treatment regimens for said patient; and (d)computer readable program code means for generating advisory informationfor one or more therapeutic treatment regimens in said ranked listingbased on said patient information and said expert rules.
 46. A computerprogram product according to claim 45, further comprising:(e) computerreadable program code means for entering a user-defined therapeutictreatment regimen for said disease or medical condition that is notgenerated or displayed via said first knowledge base; (f) computerreadable program code means for generating advisory information for saiduser-defined combination therapeutic treatment regimen.
 47. A computerprogram product according to claim 46, further comprising:(g) computerreadable program code means for entering a non-recommended therapeutictreatment regimen for said disease or medical condition that is includedin said first knowledge base but not recommended from said rankedlisting; and (h) computer readable program code means for generatingadvisory information for said non-recommended therapeutic treatmentregimen, said advisory information including at least one reason fornon-recommendation of said therapeutic treatment regimen.
 48. A computerprogram product according to claim 45, said patient informationcomprising gender, age, weight, CD4 information, viral load information,HIV genotype and phenotype information, hemoglobin information,neuropathy information, neutrophil information, pancreatitis, hepaticfunction, renal function, drug allergy and intolerance information. 49.A computer program product according to claim 45, said patientinformation including prior therapeutic treatment regimen information.50. A computer program product according to claim 45, wherein saidpatient information includes prior patient information.
 51. A computerprogram product according to claim 45, said advisory informationincluding:warnings to take the patient off a contraindicated drug beforeinitiating a corresponding therapeutic treatment regimen; andinformation clinically useful to implement a corresponding therapeutictreatment regimen.
 52. A computer program product according to claim 45wherein said computer readable program code means comprises computerreadable program code means for generating a fourth knowledge basecomprising patient therapeutic treatment regimen history, said advisoryinformation including previous therapeutic treatment regimen informationextracted from said fourth knowledge base.
 53. A computer programproduct according to claim 51, wherein said known disease or medicalcondition is HIV-1 infection, said therapeutic treatment regimenincludes antiretroviral drugs, and said therapeutic treatment regimenincludes contraindicated or potentially adversely interactingnon-antiretroviral drugs.
 54. A computer program product according toclaim 51, wherein said therapeutic treatment regimen includes a proteaseinhibitor, and said contraindicated drug is terfenadine.
 55. A computerprogram product according to claim 51, wherein said therapeutictreatment regimen includes indinavir and said contraindicated drug iscisapride.
 56. A computer program product according to claim 45, whereinsaid known disease or medical condition is one where multipleprophylactic therapeutic treatment regimens are available to be usedsingly or in combination in the treatment of said disease or medicalcondition.
 57. A computer program product according to claim 45, whereinsaid known disease or medical condition is a cardiovascular disease. 58.A computer program product according to claim 45, wherein said knowndisease or medical condition is a pulmonary disease.
 59. A computerprogram product according to claim 45, wherein said known disease ormedical condition is a neurologic disease.
 60. A computer programproduct according to claim 45, wherein said known disease or medicalcondition is cancer.
 61. A computer program product according to claim45, wherein said known disease or medical condition is a urinary tractinfection.
 62. A computer program product according to claim 45, whereinsaid known disease or medical condition is hepatitis.
 63. A computerprogram product according to claim 45, wherein said known disease ormedical condition is HIV-1 infection.
 64. A computer program productaccording to claim 45, wherein said first knowledge base comprises aplurality of different combination therapeutic treatment regimens.
 65. Acomputer program product according to claim 45, wherein drug dosageinformation is recommended and adjusted if necessary depending upon saidpatient information.
 66. A computer program product according to claim45, further comprising:(e) computer readable program code means foraccessing information for one or more therapeutic treatment regimensfrom a standard drug reference source.